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Translational Research: the Journal of Laboratory and Clinical Medicine

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https://www.readbyqxmd.com/read/28219716/genetic-regulation-of-differentially-methylated-genes-in-visceral-adipose-tissue-of-severely-obese-men-discordant-for-the-metabolic-syndrome
#1
Frédéric Guénard, André Tchernof, Yves Deshaies, Simon Biron, Odette Lescelleur, Laurent Biertho, Simon Marceau, Louis Pérusse, Marie-Claude Vohl
A genetic influence on methylation levels has been reported and methylation quantitative trait loci (meQTL) have been identified in various tissues. The contribution of genetic and epigenetic factors in the development of the metabolic syndrome (MetS) has also been noted. To pinpoint candidate genes for testing the association of SNPs with MetS and its components, we aimed to evaluate the contribution of genetic variations to differentially methylated CpG sites in severely obese men discordant for MetS. A genome-wide differential methylation analysis was conducted in visceral adipose tissue (VAT) of 31 severely obese men discordant for MetS (16 with and 15 without MetS) and identified ∼17,800 variable CpG sites...
February 2, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28130064/cardiovascular-consequences-of-metabolic-syndrome
#2
REVIEW
Johnathan D Tune, Adam G Goodwill, Daniel J Sassoon, Kieren J Mather
The metabolic syndrome (MetS) is defined as the concurrence of obesity-associated cardiovascular risk factors including abdominal obesity, impaired glucose tolerance, hypertriglyceridemia, decreased HDL cholesterol, and/or hypertension. Earlier conceptualizations of the MetS focused on insulin resistance as a core feature, and it is clearly coincident with the above list of features. Each component of the MetS is an independent risk factor for cardiovascular disease and the combination of these risk factors elevates rates and severity of cardiovascular disease, related to a spectrum of cardiovascular conditions including microvascular dysfunction, coronary atherosclerosis and calcification, cardiac dysfunction, myocardial infarction, and heart failure...
January 9, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28081931/neurogenin-2-transduced-human-neural-progenitor-cells-attenuate-neonatal-hypoxic-ischemic-brain-injury
#3
Il-Shin Lee, Kyo Yeon Koo, Kwangsoo Jung, Miri Kim, Il-Sun Kim, Kyujin Hwang, Seokhwan Yun, Haejin Lee, Jeong Eun Shin, Kook In Park
Neonatal hypoxic-ischemic (HI) brain injury leads to high mortality and neurodevelopmental disabilities. Multipotent neural progenitor cells (NPCs) with self-renewing capacity have the potential to reduce neuronal loss and improve the compromised environment in the HI brain injury. However, the therapeutic efficacy of neuronal-committed progenitor cells and the underlying mechanisms of recovery are not yet fully understood. Therefore, this study investigated the regenerative ability and action mechanisms of neuronally committed human NPCs (hNPCs) transduced with neurogenin-2 (NEUROG2) in neonatal HI brain injury...
December 29, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28087261/dna-aptamer-probes-for-detection-of-estrogen-receptor-%C3%AE-positive-carcinomas
#4
Arghya Sett, Bibhuti Bhusan Borthakur, Jagannath Dev Sharma, Amal Chandra Kataki, Utpal Bora
Estrogen receptor alpha (ERα) which is a ligand-activated transcription factor also known as NR3A1 (nuclear receptor subfamily 3, group A, member 1). It is an important biomarker for breast cancer metastasis. In the present study, we report a novel DNA aptamer candidate against estrogen receptor (ER) alpha structure. The enriched aptamer candidate was obtained after 14 iterative cycles of in vitro protein-SELEX process. Isothermal calorimetry study suggests the nanomolar sensitivity of the candidate ER_Apt1 to its target protein...
December 25, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28068521/hiv-and-its-relationship-to-insulin-resistance-and-lipid-abnormalities
#5
REVIEW
Lemuel R Non, Gerome V Escota, William G Powderly
Antiretroviral therapy has revolutionized the care of people with human immunodeficiency virus (HIV) by reducing morbidity and mortality from acquired immunodeficiency syndrome-related conditions. Despite longer life expectancy, however, HIV-infected individuals continue to have a higher risk of death compared with the general population. This has been attributed to the increasing incidence of noncommunicable diseases, in particular, atherosclerotic cardiovascular diseases. This is driven, in part, by the emergence of metabolic disorders, particularly dyslipidemia, insulin resistance, and lipodystrophy, in those on antiretroviral therapy...
December 23, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28056336/the-clinical-role-of-circulating-free-tumor-dna-in-gastrointestinal-malignancy
#6
REVIEW
Jessica A Howell, Shahid A Khan, Susanne Knapp, Mark R Thursz, Rohini Sharma
Circulating cell-free DNA (cfDNA) is DNA released from necrotic or apoptotic cells into the bloodstream. While both healthy cells and cancer cells release cfDNA, tumors are associated with higher levels of tumor-derived circulating cell-free DNA (ctDNA) detectable in blood. Absolute levels of ctDNA and its genetic mutations and epigenetic changes show promise as potentially useful biomarkers of tumor biology, progression, and response to therapy. Moreover, studies have demonstrated the discriminative accuracy of ctDNA levels for diagnosis of gastrointestinal cancer compared with benign inflammatory diseases...
December 22, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28034761/bile-acid-receptor-tgr5-overexpression-is-associated-with-decreased-intestinal-mucosal-injury-and-epithelial-cell-proliferation-in-obstructive-jaundice
#7
Chen-Guang Ji, Xiao-Li Xie, Jie Yin, Wei Qi, Lei Chen, Yun Bai, Na Wang, Dong-Qiang Zhao, Xiao-Yu Jiang, Hui-Qing Jiang
Bile acids stimulate intestinal epithelial proliferation in vitro. We sought to investigate the role of the bile acid receptor TGR5 in the protection of intestinal epithelial proliferation in obstructive jaundice. Intestinal tissues and serum samples were obtained from patients with malignant obstructive jaundice and from bile duct ligation (BDL) rats. Intestinal permeability and morphological changes in the intestinal mucosa were observed. The functions of TGR5 in cell proliferation in intestinal epithelial injury were determined by overexpression or knockdown studies in Caco-2 and FHs 74 Int cells pretreated with lipopolysaccharide (LPS)...
December 18, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28034760/insulin-resistance-in-alzheimer-s-disease
#8
REVIEW
Thomas Diehl, Roger Mullins, Dimitrios Kapogiannis
The links between systemic insulin resistance (IR), brain-specific IR, and Alzheimer's disease (AD) have been an extremely productive area of current research. This review will cover the fundamentals and pathways leading to IR, its connection to AD via cellular mechanisms, the most prominent methods and models used to examine it, an introduction to the role of extracellular vesicles (EVs) as a source of biomarkers for IR and AD, and an overview of modern clinical studies on the subject. To provide additional context, we also present a novel analysis of the spatial correlation of gene expression in the brain with the aid of Allen Human Brain Atlas data...
December 13, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28034759/targeting-p-selectin-glycoprotein-ligand-1-p-selectin-interactions-as-a-novel-therapy-for-metabolic-syndrome
#9
REVIEW
Madhukar S Patel, David Miranda-Nieves, Jiaxuan Chen, Carolyn A Haller, Elliot L Chaikof
Obesity-induced insulin resistance and metabolic syndrome continue to pose an important public health challenge worldwide as they significantly increase the risk of type 2 diabetes and atherosclerotic cardiovascular disease. Advances in the pathophysiologic understanding of this process has identified that chronic inflammation plays a pivotal role. In this regard, given that both animal models and human studies have demonstrated that the interaction of P-selectin glycoprotein ligand-1 (PSGL-1) with P-selectin is not only critical for normal immune response but also is upregulated in the setting of metabolic syndrome, PSGL-1/P-selectin interactions provide a novel target for preventing and treating resultant disease...
December 9, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28027930/tocilizumab-improves-the-proatherothrombotic-profile-of-rheumatoid-arthritis-patients-modulating-endothelial-dysfunction-netosis-and-inflammation
#10
P Ruiz-Limón, R Ortega, I Arias de la Rosa, M C Abalos-Aguilera, C Perez Sanchez, Y Jimenez Gomez, E Peralbo-Santaella, P Font, D Ruiz-Vilches, G Ferrin, E Collantes-Estevez, A Escudero, C H López Pedrera, N Barbarroja
Tocilizumab (TCZ) is an effective treatment for rheumatoid arthritis (RA). However, the changes that occurred after TCZ therapy on endothelial dysfunction, monocyte activity, NETosis, and oxidative stress, the principal effectors of atherosclerosis and cardiovascular disease, have not been analyzed yet. A total of 20 RA patients received 162 mg per week subcutaneous TCZ for 6 months. Endothelial function was measured through postocclusive hyperemia using Laser Doppler. Oxidative stress markers in monocytes and neutrophils were analyzed by flow cytometry...
December 9, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28027929/nrf2-exerts-cell-autonomous-antifibrotic-effects-compromised-function-in-systemic-sclerosis-and-therapeutic-rescue-with-a-novel-heterocyclic-chalcone-derivative
#11
Jun Wei, Hongyan Zhu, Gabriel Lord, Mitra Bhattachayya, Brielle M Jones, Graham Allaway, Shyam S Biswal, Benjamin Korman, Roberta G Marangoni, Warren G Tourtellotte, John Varga
The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) governs antioxidant, innate immune and cytoprotective responses and its deregulation is prominent in chronic inflammatory conditions. To examine the hypothesis that Nrf2 might be implicated in systemic sclerosis (SSc), we investigated its expression, activity, and mechanism of action in SSc patient samples and mouse models of fibrosis and evaluated the effects of a novel pharmacologic Nrf2 agonist. We found that both expression and activity of Nrf2 were significantly reduced in SSc patient skin biopsies and showed negative correlation with inflammatory gene expression...
December 9, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28025032/the-metabolic-syndrome-and-chronic-kidney-disease
#12
REVIEW
Xin Zhang, Lilach O Lerman
The metabolic syndrome (MetS) is a cluster of cardiovascular risk factors including insulin resistance (IR), dyslipidemia, and hypertension, which may also foster development of chronic kidney disease. The mechanisms of MetS-induced kidney disease are not fully understood. The purpose of this review is to summarize recent discoveries regarding the impact of MetS on the kidney, particularly on the renal microvasculature and cellular mitochondria. Fundamental manifestations of MetS include IR and adipose tissue expansion, the latter promoting chronic inflammation and oxidative stress that exacerbate IR...
December 9, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28011152/adenosine-a2a-receptor-stimulation-blocks-development-of-nonalcoholic-steatohepatitis-in-mice-by-multilevel-inhibition-of-signals-that-cause-immunolipotoxicity
#13
Elisa Alchera, Simona Rolla, Chiara Imarisio, Valentina Bardina, Guido Valente, Francesco Novelli, Rita Carini
Lipotoxicity and immunoinflammation are associated with the evolution of steatosis toward nonalcoholic steatohepatitis (NASH). This study reports the ability of adenosine A2a receptor (A2aR) activation to inhibit NASH development by modulating the responses of CD4(+) T-helper (Th) cells to avoid an immuno-mediated potentiation of lipotoxicity. The effect of the A2aR agonist CGS21680 on immunoinflammatory signals, CD4(+)Th cell infiltration and immunolipotoxicity was analyzed in steatotic C57BL/6 mice fed with a methionine-choline-deficient (MCD) diet and in mouse hepatocytes exposed to palmitic acid (PA)...
December 6, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/27986604/cell-therapy-for-the-degenerating-intervertebral-disc
#14
REVIEW
Wei Tong, Zhouyu Lu, Ling Qin, Robert L Mauck, Harvey E Smith, Lachlan J Smith, Neil R Malhotra, Martin F Heyworth, Franklin Caldera, Motomi Enomoto-Iwamoto, Yejia Zhang
Spinal conditions related to intervertebral disc (IVD) degeneration cost billions of dollars in the US annually. Despite the prevalence and soaring cost, there is no specific treatment that restores the physiological function of the diseased IVD. Thus, it is vital to develop new treatment strategies to repair the degenerating IVD. Persons with IVD degeneration without back pain or radicular leg pain often do not require any intervention. Only patients with severe back pain related to the IVD degeneration or biomechanical instability are likely candidates for cell therapy...
November 28, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/27593097/optimizing-hemoglobin-thresholds-for-detection-of-iron-deficiency-among-reproductive-age-women-in-the-united-states
#15
Deepa L Sekhar, Allen R Kunselman, Cynthia H Chuang, Ian M Paul
Iron deficiency (ID) affects 9%-16% of US women with well-documented morbidity in academic performance, mood, and concentration. Current ID screening depends on the detection of low hemoglobin (ie, anemia, <12.0 g/dL). However, anemia is a late-stage indicator of ID. The study hypothesis was that using higher hemoglobin thresholds would optimize ID screening. The objective was to assess the sensitivity and specificity of hemoglobin to detect ID among nonpregnant, reproductive-age women of 12-49 years and to determine if psychometric characteristics varied by age and race...
February 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/27567430/potentiation-and-tolerance-of-toll-like-receptor-priming-in-human-endothelial-cells
#16
Stephen R Koch, Fred S Lamb, Judith Hellman, Edward R Sherwood, Ryan J Stark
Repeated challenge of lipopolysaccharide (LPS) alters the response to subsequent LPS exposures via modulation of toll-like receptor 4 (TLR4). Whether activation of other TLRs can modulate TLR4 responses, and vice versa, remains unclear. Specifically with regards to endothelial cells, a key component of innate immunity, the impact of TLR cross-modulation is unknown. We postulated that TLR2 priming (via Pam3Csk4) would inhibit TLR4-mediated responses while TLR3 priming (via Poly I:C) would enhance subsequent TLR4-inflammatory signaling...
February 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/27543902/epigenetic-contribution-of-the-myosin-light-chain-kinase-gene-to-the-risk-for-acute-respiratory-distress-syndrome
#17
Keely L Szilágyi, Cong Liu, Xu Zhang, Ting Wang, Jeffrey D Fortman, Wei Zhang, Joe G N Garcia
Acute respiratory distress syndrome (ARDS) is a devastating clinical syndrome with a considerable case fatality rate (∼30%-40%). Health disparities exist with African descent (AD) subjects exhibiting greater mortality than European descent (ED) individuals. Myosin light chain kinase is encoded by MYLK, whose genetic variants are implicated in ARDS pathogenesis and may influence ARDS mortality. As baseline population-specific epigenetic changes, that is, cytosine modifications, have been observed between AD and ED individuals, epigenetic variations in MYLK may provide insights into ARDS disparities...
February 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/27832936/feeding-the-microbiota-gut-brain-axis-diet-microbiome-and-neuropsychiatry
#18
REVIEW
Kiran V Sandhu, Eoin Sherwin, Harriët Schellekens, Catherine Stanton, Timothy G Dinan, John F Cryan
The microbial population residing within the human gut represents one of the most densely populated microbial niche in the human body with growing evidence showing it playing a key role in the regulation of behavior and brain function. The bidirectional communication between the gut microbiota and the brain, the microbiota-gut-brain axis, occurs through various pathways including the vagus nerve, the immune system, neuroendocrine pathways, and bacteria-derived metabolites. This axis has been shown to influence neurotransmission and the behavior that are often associated with neuropsychiatric conditions...
January 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/27832935/the-microbiome-and-human-disease-pathogenesis-how-do-you-do-what-you-do-to-me-%C3%A2
#19
Edward N Janoff
No abstract text is available yet for this article.
January 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/27686718/microbiome-and-food-allergy
#20
REVIEW
Ana B Blázquez, M Cecilia Berin
Food allergy is a common disease affecting approximately 8% of children and 5% of adults. The prevalence has increased over the last two decades, suggesting an important environmental contribution to susceptibility. Studies have identified mode of birth, pet exposure, and having older siblings as being significant risk modifying factors in the development of food allergy. With the discovery that these factors significantly impact the composition of the intestinal microbiome, which is known to play a critical role in shaping the immune system, recent studies have begun to address the role of the intestinal microbiota in the development of food allergy...
January 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
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